Ischemic diseases such as thrombosis or arteriosclerosis may break out and become worse by a complicated interaction of three factors of the change in the components in the blood fluid, the abnormal blood flow and the disorder of the blood vessel wall. Although thrombosis is caused by various factors, it mainly breaks out by the disorder of the intima cells like in the case of atherosclerosis, subsequently the activation of platelets, and then by the adhesion and aggregation of platelets.
Arteriosclerosis breaks out and becomes worse by the growth of the blood vessel smooth muscle cells by the complicated interaction of the above mentioned three factors, and then by the thickening of the intima.
Thus, it is very important that a medicant being useful in the prophylaxis or treatment of ischemic diseases such as thrombosis or arteriosclerosis should essentially show both antithrombotic activity and intima thickening inhibitory activity.
There are known various carbostyril derivatives. For example, WO 93/04042 (=JP-A-5-194405) discloses carbostyril derivatives of the formula: ##STR2## wherein A is a lower alkylene; R is --NR.sup.1 R.sup.2, --SO.sub.2 NR.sup.3 R.sup.4, or --Y--NR.sup.5 R.sup.6 ; R.sup.1 is --(CO).sub.1 --B--(CO).sub.m --NR.sup.7 R.sup.8 or --SO.sub.2 --D--R.sup.9 ; R.sup.2 is H, a cycloalkyl, a substituted or unsubstituted phenyl, etc.; or R.sup.1 and R.sup.2 may combine with the adjacent nitrogen to form a substituted or unsubstituted pyrrolidinyl; R.sup.3 is H, lower alkyl, --E--(CO).sub.n --NR.sup.10 R.sup.11, etc.; R.sup.4 is H, a cycloalkyl, a substituted or unsubstituted phenyl, a heterocyclic group-substituted alkyl, etc.; Y is --NHCO--, --NHC(=S)--or --C(.dbd.S)--; R.sup.5 and R.sup.6 are each H, a lower alkyl, a cycloalkyl, a piperidinyl-alkyl, etc.; and W is O or S, which have a platelet aggregation inhibitory activity and a platelet adhesion inhibitory activity. Some compounds inclusive in the general formula of the present invention may fall within the scope of the general formula of this prior art, and those possibly overlapping compounds are excluded from the present invention by the proviso phrase.
U.S. Pat. Nos. 4,070,470, 4,216,220 and 4,313,947 disclose carbostyril derivatives of the formula: ##STR3## wherein R.sup.1 is H, lower alkyl, lower alkenyl or aralkyl, R.sup.4 is OH, alkoxy, substituted or unsubstituted amino, heterocyclic amino, etc., A is lower alkylene or vinylene, B is --CH.sub.2 --, --CH.sub.2 CH.sub.2 -- or --CH.dbd.CH--, and m and n are 0 or a positive integer with m+n being no more than 11, which have a platelet ag gregation inhibitory activity.
U.S. Pat. No. 4,298,739 discloses carbostyril derivatives of the formula: ##STR4## wherein R.sup.1 is H, lower alkyl, lower alkenyl or phenylalkyl, R.sup.2 is H, halogen, OH or phenylalkoxy, R.sup.3 is H, OH or lower alkyl, R.sup.4 is cycloalkyl, substituted or unsubstituted phenyl, cycloalkylalkyl, etc., R.sup.5 is H, alkyl, lower alkenyl, phenyl, cycloalkyl, etc., m is 1-3, and l and n are 0 or an integer of 1-7, which have a platelet aggregation inhibitory activity.
U.S. Pat. No. 4,435,404 discloses carbostyril derivatives of the formula: ##STR5## wherein R.sup.1 is H, R.sup.2 is H or lower alkyl, R.sup.3 is hydroxy-lower alkyl having 1 to 3 hydroxy groups, lower alkanoyloxy-lower alkyl, etc., R.sup.4 is cycloalkyl having 1 to 3 hydroxy groups, etc., or R.sup.3 and R.sup.4 form a group of the formula: ##STR6## (R.sup.3 is phenyl, etc.), A is lower alkylene, which have a platelet aggregation inhibitory activity.
EP-A-0450066 (published on Oct. 9, 1989) discloses carbostyril derivatives of the formula: ##STR7## wherein R.sup.1 is substituted or unsubstituted cycloalkyl-lower alkyl, cycloalkyl, substituted or unsubstituted phenyl, piperidinyl-lower alkyl, etc., R.sup.2 is substituted or unsubstituted heterocyclo-lower alkyl, pyridylthio-lower alkyl, substituted or unsubstituted lower alkyl, etc., and A is an alkylene, which have a platelet aggregation inhibitory activity.
JP-A-55-79371 (published on Jun. 14, 1980) discloses carbostyril derivatives of the formula: ##STR8## wherein R.sup.1 is lower alkyl, R.sup.2 is oxo-substituted cycloalkyl, which have a platelet aggregation inhibitory activity.
JP-A-57-14574 (published on Jan. 25, 1982) discloses carbostyril derivatives of the formula: ##STR9## wherein R.sup.1 is lower alkyl, R.sup.2 is cycloalkyl or pyridyl, and A is an alkylene, which have a platelet aggregation inhibitory activity.
There are many other literatures which disclose carbostyril derivatives analogous to the compounds of the present invention.
However, those carbostyril derivatives of those known literatures as mentioned above are distinguished from the compounds of the present invention in that those known compounds other than those of the above first literature WO 93/04042 have no ureido-lower alkoxy substituent on the carbostyril nucleus.